Futibatinib in Combination With Durvalumab Prior to Cystectomy for the Treatment of Muscle-Invasive Bladder Cancer Patients Who Are Ineligible for Cisplatin-based Therapy

NCT06263153 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: OSU-23329NCI-2024-00002
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 3

Brief Summary

This phase II trial tests how well the combination of futibatinib and durvalumab given before cystectomy works in treating patients with muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin-based therapy. Cisplatin-based therapy is the standard of care for patients with MIBC. However, many patients cannot receive standard therapy due to poor renal function, peripheral neuropathy, poor functional status, or clinically significant heart failure. Futibatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Durvalumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Radical cystectomy is a surgery to remove all of the bladder as well as nearby tissues and organs. Giving futibatinib in combination with durvalumab before surgery may be an effective treatment option for patients with MIBC who are ineligible for cisplatin-based therapy.

Conditions

Bladder Urothelial Carcinoma; Muscle Invasive Bladder Carcinoma; Stage II Bladder Cancer AJCC v8; Stage IIIA Bladder Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Complete pathologic response rate

  Will be defined by a percentage of participants with ypT0N0 by pathologic responses.

  1 day (At the time of radical cystectomy)

Secondary Outcomes (5)

• Incidence of adverse events (AEs)

  Up to 30 days after cystectomy/end of treatment

• Pathologic down-staging rate to non-muscle invasive disease

  1 day (At the time of radical cystectomy)

• Overall survival

  Time from the start date of treatment to death on the study from any cause, assessed up to 2 years

• Progression free survival

  Time from the start date of treatment to the first occurrence of disease progression or death on the study from any cause, whichever occurs earlier, assessed up to 2 years

• Frequency and severity of adverse events, including delay in cystectomy

  Up to 60 days after cystectomy/end of treatment

Study Arms (1)

Treatment (futibatinib, durvalumab, radical cystectomy)

EXPERIMENTAL

Patients receive futibatinib PO QD on days 1-28 and durvalumab IV over 60 minutes on day 1 of each cycle. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo radical cystectomy within 4-12 weeks. Patients also undergo CT and MRI during screening and on the trial and also undergo blood sample collection on the trial.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Biological: Durvalumab; Drug: Futibatinib; Procedure: Magnetic Resonance Imaging; Procedure: Radical Cystectomy

Interventions

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT Scan, tomography

Treatment (futibatinib, durvalumab, radical cystectomy)

Durvalumab BIOLOGICAL

Given IV

Also known as: Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736

Treatment (futibatinib, durvalumab, radical cystectomy)

Futibatinib DRUG

Given PO

Also known as: Lytgobi, TAS-120

Treatment (futibatinib, durvalumab, radical cystectomy)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (futibatinib, durvalumab, radical cystectomy)

Radical Cystectomy PROCEDURE

Undergo radical cystectomy

Also known as: Complete Cystectomy

Treatment (futibatinib, durvalumab, radical cystectomy)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (futibatinib, durvalumab, radical cystectomy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to provide signed informed consent
• Female or male subjects \>= 18 years old
• Bodyweight \>30kg
• FGFR1, 2, or 3 overexpression as defined by a score of 3+ or 4+ on ribonucleic acid (RNA) in-situ hybridization (RNAScope assay)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Histologically confirmed urothelial carcinoma of the bladder
• Mixed histologies are permitted if urothelial carcinoma is the predominant histology ( \>= 50%)
• Clinical stage T2-T4a, N0, M0 disease by trans urethral removal of bladder tumour (TURBT) and imaging studies (stage II-IIIA per American Joint Committee on Cancer \[AJCC\] 2018)
• Refuse or ineligible for cisplatin-based neoadjuvant chemotherapy as defined by any of the following:
• ECOG performance status (PS) \> 1
• Creatinine clearance (calculated or measured) \< 60 mL/min as measured by the Cockcroft-Gault formula
• Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v 5.0) grade \>= 2 hearing loss
• CTCAE v 5.0 grade \>= 2 neuropathy
• New York Heart Association (NYHA) class \> II cardiac dysfunction
• Treatment with anti-PD-1/PD-L1 therapy for non-muscle invasive bladder cancer (NMIBC) is permitted if it is completed \> 3 months before registration

You may not qualify if:

• Women who are pregnant or breastfeeding
• Male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy
• Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks before the first dose of trial treatment
• Has upper tract urothelial carcinoma
• Has small-cell carcinoma component on histology
• Evidence of measurable nodal or metastatic disease
• Concurrent anticancer therapy (e.g., chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, hormonal therapy, investigational therapy, intravesical therapy, or tumor embolization)
• Received prior systemic chemotherapy for muscle-invasive bladder cancer at any time in the patient's medical history
• Has received anti-PD-1/PD-L1 therapy or FGFR inhibitor previously for MIBC, except if used in earlier stage urothelial carcinoma such as non-muscle invasive bladder cancer (NMIBC) and completed \> 3 months prior to registration
• Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy.
• All AEs while receiving prior immunotherapy must have completely resolved or resolved to baseline prior to screening for this study.
• Must not have experienced a ≥Grade 3 immune related AE or an immune related neurologic or ocular AE of any grade while receiving prior immunotherapy. NOTE: Patients with endocrine AE of ≤Grade 2 are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic.
• Must not have required the use of additional immunosuppression other than corticosteroids for the management of an AE, not have experienced recurrence of an AE if re-challenged, and not currently require maintenance doses of \> 10 mg prednisone or equivalent per day.
• Underwent major surgery and has not recovered adequately from the intervention's toxicity and/or complications before starting therapy
• Has an active second malignancy except for low-risk localized prostate cancer on "watch and wait"

Sponsors & Collaborators

• Yuanquan Yang: lead
• Gateway for Cancer Research: collaborator

Study Sites (3)

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

WITHDRAWN

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44195, United States

RECRUITING

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

Related Links

• The Jamesline

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Specimen Handling; durvalumab; Immunoglobulin G; Disulfides; futibatinib; Magnetic Resonance Spectroscopy; Cystectomy

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals; Spectrum Analysis; Chemistry Techniques, Analytical; Urologic Surgical Procedures; Urogenital Surgical Procedures; Surgical Procedures, Operative

Study Officials

• Yuanquan Yang, MD, PhD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

The Ohio State Comprehensive Cancer Center

CONTACT

800-293-5066; GUResearchCoordinators@osumc.edu

Rebecca Williams

CONTACT

614-366-0959; Rebecca.Williams3@osumc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 8, 2024
• First Posted: February 16, 2024
• Study Start: December 30, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: December 17, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)